1. Field Of The Invention
The invention relates to N-5-protected 2,5-diamino-4,6-dichloropyrimidines of the general formula: ##STR2## wherein R is an alkoxy group or a trifluoromethyl group, as well as a process for their production. These compounds form valuable intermediate products for the production of antiviral nucleotide derivatives--see PCT Published Application WO 91/01310.
2. Background Art
Various syntheses for the production of 2,5-diamino-4,6-dichloropyrimidines are known. Thus, Legraverend et al. in "Synthesis", (1990), pages 587 to 589, reports that an amino malonic acid ethyl ester can be cyclized with guanidine in the presence of sodium alcoholate to 4,6-dihydroxy-2,5-diaminopyrimidine with a yield of 64 percent. The dihydroxypyrimidine is then reacted to the desired dichloropyrimidine with phosphorus oxychloride/phosphorus(V)-chloride in the presence of a quaternary ammonium salt under drastic reaction conditions with a yield of 32 percent.
Legraverend et al. indicates that the chlorination with phosphorus oxychloride takes place unsuccessfully. But the necessity of additional reagents such as phosphorus(V)chloride, of quaternary ammonium salts or of drastic reaction conditions and the thus achievable modest yields, is an obvious drawback of this synthesis. A sudden improvement of the synthesis was disclosed in PCT Application W091/01310. The chlorination step of 4,6-dihydoxy-2,5-diaminopyridine to the desired 4,6-dichloro derivative is performed in PCT Application W091/01310 with phosphorus oxychloride alone as the chlorination agent in the presence of a quaternary ammonium chloride or a hydrochloride of a tertiary amine. The yields were able to be increased to 50 to 60 percent. But the use of substantial amounts of ammonium salts or amino salts, that result as salt load and have to be fed to a waste disposal still constitute a considerable drawback.